18.4 Prescription & Over-the-Counter Substance Misuse: Opioids, Stimulants, Kratom & DXM
Key Takeaways
- Prescription drug misuse is the first example named in the blueprint's other use disorders category, covering opioid analgesics, stimulants, sedatives and over-the-counter agents.
- Kratom contains mitragynine and 7-hydroxymitragynine, partial mu-opioid agonists that produce a genuine opioid withdrawal syndrome and respond to buprenorphine.
- 7-hydroxymitragynine concentrates sold as semi-synthetic products are far more potent than leaf kratom and have driven a rise in dependence presentations.
- High-dose loperamide causes torsades de pointes and other ventricular dysrhythmias through cardiac sodium and potassium channel blockade, and is used both to self-treat opioid withdrawal and to achieve euphoria.
- Dextromethorphan misuse causes NMDA-antagonist dissociation and serotonin toxicity, and combination products add acetaminophen hepatotoxicity risk.
18.4 Prescription & Over-the-Counter Substance Misuse: Opioids, Stimulants, Kratom & DXM
Quick Answer: The blueprint's category E names prescription drugs first. Beyond diverted opioids, stimulants and sedatives, the APRN must know kratom (mitragynine and 7-hydroxymitragynine — partial mu agonists producing true opioid withdrawal, responsive to buprenorphine), high-dose loperamide (sodium and potassium channel blockade causing torsades de pointes), dextromethorphan (NMDA antagonism plus serotonin toxicity, with acetaminophen hepatotoxicity in combination products), gabapentinoids (potentiate opioid respiratory depression), and anabolic-androgenic steroids (hypogonadism and mood instability). None of these appear on a routine urine drug screen.
1. Diverted Prescription Medications
| Class | Diversion pattern | APRN response |
|---|---|---|
| Opioid analgesics | Leftover supplies from family or friends remain the most common source for first non-medical use | Prescribe the smallest effective quantity; teach safe storage and disposal; review the PDMP |
| Prescription stimulants | Misuse concentrated among students and young adults for performance; diversion from legitimately prescribed peers | Confirm diagnosis before prescribing; use long-acting formulations; count-and-verify; PDMP at every refill |
| Benzodiazepines and Z-drugs | Frequently obtained from multiple prescribers or illicit markets; counterfeit "alprazolam" pills commonly contain fentanyl or a novel benzodiazepine | Avoid co-prescribing with opioids; taper rather than abruptly stop; counsel on counterfeit pill risk |
| Quetiapine | Misused for sedation, including in correctional settings | Recognize non-therapeutic requests; substitute evidence-based options for insomnia |
Counterfeit-pill counseling is now essential. A pill that looks like a 30 mg oxycodone or a 2 mg alprazolam and did not come from a pharmacy should be assumed to contain illicitly manufactured fentanyl. This single teaching point is among the highest-yield overdose-prevention messages available.
2. Kratom (Mitragyna speciosa)
| Element | Detail |
|---|---|
| Active alkaloids | Mitragynine (partial mu agonist, stimulant-like at low doses) and 7-hydroxymitragynine (far more potent mu agonist) |
| Dose-dependent effect | Low dose: stimulant-like alertness and sociability. High dose: opioid-like analgesia and sedation |
| Why people use it | Self-treatment of opioid withdrawal, chronic pain, fatigue and depression; legal and available in gas stations and smoke shops in most states |
| Dependence | Genuine physical dependence with a true opioid withdrawal syndrome: myalgias, rhinorrhea, diarrhea, restlessness, insomnia, irritability |
| Treatment | Buprenorphine treats kratom withdrawal and kratom use disorder effectively — a high-yield and frequently missed point |
| Toxicity | Seizures, hepatotoxicity (cholestatic pattern), and deaths, usually with co-ingestants |
| Semi-synthetic concentrates | Products marketed on 7-hydroxymitragynine content are far more potent than leaf kratom and have driven a surge in severe dependence; they are the subject of active federal scheduling attention |
| Detection | Not detected on standard opioid immunoassays; requires specific testing |
3. Loperamide
- An antidiarrheal and a peripherally acting mu-opioid agonist with minimal central penetration at therapeutic doses, because P-glycoprotein pumps it out of the CNS.
- At supratherapeutic doses — often 50 to 200 tablets daily — the efflux system is saturated and central opioid effects occur. Users also co-ingest P-glycoprotein and CYP3A4 inhibitors (cimetidine, quinidine, grapefruit juice) to increase brain penetration.
- Cardiotoxicity is the killer: loperamide blocks cardiac sodium channels (QRS widening, Brugada-like pattern) and potassium channels (QT prolongation), producing torsades de pointes, ventricular tachycardia and cardiac arrest.
- Management: cardiac monitoring, magnesium, sodium bicarbonate for QRS widening, overdrive pacing or isoproterenol for recurrent torsades. Naloxone reverses the opioid effect but not the cardiac channel blockade.
- Clinical clue: a patient with opioid use disorder, a wide QRS and a prolonged QT with no other explanation. Ask directly about over-the-counter antidiarrheals.
4. Dextromethorphan
- At high doses, DXM and its metabolite dextrorphan are NMDA antagonists, producing dose-dependent "plateaus" from mild euphoria to full dissociation resembling PCP.
- Serotonin toxicity risk is real, especially combined with SSRIs, MAOIs, linezolid or tramadol.
- CYP2D6 poor metabolizers achieve much higher dextromethorphan concentrations, and CYP2D6 inhibitors such as fluoxetine, paroxetine and bupropion have the same effect.
- Combination products are the main hazard: cough and cold preparations containing acetaminophen (hepatotoxicity), chlorpheniramine (anticholinergic toxicity) or pseudoephedrine (sympathomimetic toxicity). Always check the full ingredient list.
- Peak use is among adolescents, for whom access is trivial — another reason to ask explicitly about over-the-counter products.
5. Gabapentinoids
| Point | Detail |
|---|---|
| Mechanism | Bind the alpha-2-delta subunit of voltage-gated calcium channels |
| Misuse | Produces euphoria and potentiates opioid effect; widely misused in populations with opioid use disorder and in correctional settings |
| Mortality signal | Concurrent gabapentinoid use increases opioid-related respiratory depression and overdose death risk |
| Scheduling | Pregabalin is federally Schedule V; gabapentin is not federally scheduled but is a controlled substance in a growing number of states |
| Withdrawal | Abrupt discontinuation after chronic high-dose use can cause agitation, diaphoresis, confusion and seizures — taper rather than stop |
6. Anabolic-Androgenic Steroids and Other Agents
| Agent | Key clinical points |
|---|---|
| Anabolic-androgenic steroids | Schedule III; cause hypogonadotropic hypogonadism with testicular atrophy, infertility, gynecomastia, erythrocytosis, dyslipidemia, cardiomyopathy, hepatic injury with 17-alpha-alkylated oral agents, acne, and mood instability including aggression and depression during withdrawal; withdrawal depression carries suicide risk |
| Tianeptine ("gas station heroin") | Mu-opioid agonist sold as a supplement; produces opioid dependence and withdrawal; multiple state bans |
| Phenibut | GABA-B agonist sold online; severe dependence with a benzodiazepine-like withdrawal including delirium and seizures; requires a baclofen or benzodiazepine taper |
| Promethazine with codeine ("lean") | Combination opioid and antihistamine; respiratory depression; frequently combined with alcohol |
The unifying clinical lesson: ask about supplements, gas-station products and over-the-counter medicines by name. A patient answering "no" to "do you use drugs?" may be taking 60 loperamide tablets a day or a 7-hydroxymitragynine concentrate, and the routine urine drug screen will be entirely negative.
A patient using kratom daily for two years presents with myalgias, rhinorrhea, diarrhea, restlessness and insomnia 24 hours after stopping. His urine opioid immunoassay is negative. What is the most appropriate management?
A patient with opioid use disorder presents with syncope. ECG shows a QRS of 148 milliseconds and a QTc of 610 milliseconds, and he has an episode of torsades de pointes. He denies using any prescription medication. Which question is most likely to identify the cause?
An adolescent is brought in with dissociation, agitation, hyperthermia, clonus and hyperreflexia after ingesting a large quantity of an over-the-counter cough and cold preparation while taking fluoxetine. Which two hazards must the APRN address?